Suppression of autologous mixed leukocyte reaction in type 1 diabetes mellitus by in vivo-activated T lymphocytes

Abstract Type 1 diabetes mellitus (T1DM) is an autoimmune insulin-dependent disease associated with destructive bone homeostasis. Accumulating evidence has proven that miRNAs are widely involved in the regulation of bone homeostasis. However, whether miRNAs also regulate osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) in T1DM mice is under exploration. In this study, miRNA microarray was utilized to screen the differentially expressed miRNAs, which uncovered that miR-214-3p potentially inhibited BMSCs osteogenic differentiation in T1DM mice. We found that high glucose suppressed BMSCs osteogenic differentiation with significant elevation of the miR-214-3p expression. Further study found that the osteogenic differentiation of BMSCs was inhibited by AgomiR-214-3p while enhanced by AntagomiR-214-3p in BMSCs supplemented with high glucose. Moreover, we found that miR-214-3p knockout T1DM mice were resistant to high-glucose-induced bone loss. These results provide a novel insight into an inhibitory role of high-glucose-induced miR-214-3p in BMSCs osteogenic differentiation both in vitro and in vivo. Molecular studies revealed that miR-214-3p inhibits BMSCs osteogenic differentiation by targeting the 3′-UTR of β-catenin, which was further corroborated in human bone specimens and BMSCs of T1DM patients. Taken together, our study discovered that miR-214-3p is a pivotal regulator of BMSCs osteogenic differentiation in T1DM mice. Our findings also suggest that miR-214-3p could be a potential target in the treatment of bone disorders in patients with T1DM.

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Peptide-specific cytotoxicity of T lymphocytes against glutamic acid decarboxylase and insulin in type 1 diabetes mellitus

Diabetes Research and Clinical Practice ◽

10.1016/s0168-8227(00)00225-4 ◽

2001 ◽

Vol 51 (3) ◽

pp. 173-179 ◽

Cited By ~ 13

Author(s):

Kayo Kimura ◽

Tomoyuki Kawamura ◽

Shinji Kadotani ◽

Hiroshi Inada ◽

Shizuhiro Niihira ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 1 Diabetes ◽

T Lymphocytes ◽

Glutamic Acid ◽

Type 1 Diabetes Mellitus ◽

Glutamic Acid Decarboxylase ◽

Acid Decarboxylase ◽

Specific Cytotoxicity

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The role of regulatory CD4+CD25+high T-lymphocytes and their functional activity in the development of type 1 diabetes mellitus

Diabetes Mellitus ◽

10.14341/2072-0351-5483 ◽

2010 ◽

Vol 13 (3) ◽

pp. 25-31

Author(s):

Tatiana Vasil'evna Nikonova ◽

Pavel Vasil'evich Apanovich ◽

Elena Vladimirovna Pekareva ◽

Vera Anatol'evna Gorelysheva ◽

Sergey Alexandrovich Prokof'ev ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 1 Diabetes ◽

T Lymphocytes ◽

Type 1 Diabetes Mellitus ◽

Functional Activity ◽

Risk Group ◽

Control Group ◽

Suppressor Activity ◽

Foxp3 Gene

Type 1 diabetes mellitus (DM1) is associated with compromised (defective) immunologic tolerance to autoantigens and selective destruction of pancreatic B-cells by CD4+ (effector) and CD8 (cytotoxic) lymphocytes. The mechanisms of autotolerance involve CD4+CD25+high T-regulatory cells (Treg) whose suppressor activity depends on the expression of the FoxP3 gene. Aim. Detection of quantitative and functional alterations at the level of regulation of immunity in subjects at risk of DM1 and patients with different duration of DM1. Materials and methods. 116 patients (67 men and 49 women) with different duration of DM1. The risk group was comprised of 33 subjects (10 men and 23 women), control group included 16 subjects. In all cases, HLA genotyping was performed, autoantibodies to GDC, insulin and tyrosine phosphatase, islet cell antigens were determined, subpopulation composition of CD3+, CD4+, CD8+, CD38+, HLA DR+, CD25+, CD4+25+ lymphocytes and their functional activities (FoxP3 gene expression) studied, C-peptie and HbA1c levels measured. Results. A tendency toward a rise in Cd25+ and CD4+25+ T-lymphocytes and a decrease in FoxP3 expression was documented in the risk group compared with control (p0.05) but their functional activity was lower (p

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Effects of Anonna muricata L. (soursop) seeds oil improves in model in vivo and in vitro of type 1 diabetes mellitus

Journal of Allergy and Clinical Immunology ◽

10.1016/j.jaci.2016.12.105 ◽

2017 ◽

Vol 139 (2) ◽

pp. AB15

Author(s):

Laise Cedraz Pinto ◽

Ana Tereza Cerqueira-lima ◽

Samara dos Santos Suzart ◽

Raiane Souza ◽

Bruna Tosta ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 1 Diabetes ◽

Type 1 Diabetes Mellitus

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Evaluation of efficiency of Fas-mediated apotosis of peripheral blood lymphocytes in patients with type 1 diabetes mellitus

Medical alphabet ◽

10.33667/2078-5631-2019-3-22(397)-26-32 ◽

2019 ◽

Vol 3 (22) ◽

pp. 26-32

Author(s):

A. V. Lugovaya ◽

N. M. Kalinina ◽

V. F. Mitreikin ◽

Yu. V. Emanuel ◽

Yu. P. Kovaltchuk ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 1 Diabetes ◽

High Risk ◽

T Lymphocytes ◽

Type 1 Diabetes Mellitus ◽

Peripheral Blood ◽

Peripheral Blood Lymphocytes ◽

Soluble Fas ◽

Soluble Fasl

The Fas/FasL system is known to play a central role in maintaining peripheral self-tolerance and tissue homeostasis of the organism [12, 18]. Fas-mediated apoptosis is induced by binding of the Fas(CD 95/APO-l/TNFRSF6)-receptor to the Fas(CD 95L/CD 178/TNFSF6)-ligand on the respective cells [24]. Triggering of the expression of cell surface Fas receptors (Fas) regulates the elimination of autoreactive T- and B-lymphocytes by apoptosis. It is known that impaired activation of Fas-mediated apoptosis in individual subpopulations of T-cells plays an important role in the pathogenesis of type 1 diabetes mellitus (T1DM). The main key point in the development of T1DM is resistance to apoptosis of activated autoreactive T-lymphocytes, which migrate from the bloodstream to the pancreas and take an active part in β-cells destruction. Аt the present time, most of the results on the study of Fas-mediated apoptosis in T1DM were obtained in experiments in vitro [11, 18, 31]. There is no doubt that in vivo autoimmune pathological changes are more profound, and extrapolation of the results obtained in the experiment to the organism is not always valid. Тhereby, it seems relevant to evaluate the efficiency of Fas-mediated apoptosis of T-lymphocytes in the blood of patients with T1DM, depending on the compensation phase and the duration of the disease. In the article, the markers of Fas-mediated apoptosis of peripheral blood lymphocytes in patients with type 1 diabetes mellitus and individuals with high risk of T1DM development have been studied. The surface expression of Fas in individual subpopulations of T-lymphocytes was еvaluated. The inhibition of Fas-mediated apoptosis of autoreactive CD 95+-cells by soluble Fas-receptor was detected in patients with decompensation of T1DM. In compensation phase of T1DM Fas-mediated apoptosis of lymphocyte was successfully realized via the soluble Fas ligand (sFasL). The increased level of soluble FasL was revealed in compensation phase of T1DM and in individuals with high risk of T1DM development. This probably has a protective value, since the soluble FasL is involved in the removal of the peripheral blood autoreactive CD 95+-cells.

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In vivo Labeling of Bone Microdamage in an Animal Model of Type 1 Diabetes Mellitus

Scientific Reports ◽

10.1038/s41598-019-53487-6 ◽

2019 ◽

Vol 9 (1) ◽

Author(s):

Sahar Mohsin ◽

Suneesh Kaimala ◽

Eman Khamis Yousef AlTamimi ◽

Saeed Tariq ◽

Ernest Adeghate

Keyword(s):

Diabetes Mellitus ◽

Animal Model ◽

Type 1 Diabetes ◽

Type 1 Diabetes Mellitus ◽

Bone Strength ◽

Bone Quality ◽

Increase Fracture Risk ◽

Bone Microdamage

AbstractType 1 diabetes mellitus (DM1) is linked to a decrease in bone strength. Bone strength entails both bone mineral density and bone quality. Limited data are available regarding diabetes-induced microdamage, which can severely influence bone quality. This study has investigated bone microdamage as a measure of bone quality in an animal model of DM1. Microdamage in the neck of the femur was labelled in vivo using multiple fluorochromes at 4, 12 and 24 weeks after the onset of DM1. Microcracks were quantified and their morphology analyzed using microscopy techniques. The mean length of microcracks at 24 weeks, and crack numerical and surface densities were significantly higher (p < 0.05) 4 weeks after the onset of DM1 when compared with control. Diffuse damage density was highest at 12 weeks after the onset of DM1. The arrangement of the collagen fibrils became progressively more irregular from 4 to 24 weeks of DM. This is the first study to analyze microdamage in vivo at different time points of DM1. DM1is associated with microcracks from the early stage, however bone microstructure shows toughening mechanisms that arrest their growth but disease progression further deteriorates bone quality resulting in longer microcracks which may increase fracture risk.

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